The present invention relates generally to diagnosis of a multiple sclerosis disease state in humans and more specifically to novel antigen and antibody preparations and immunological reagents containing same which are useful in diagnosis of multiple sclerosis.
Multiple sclerosis, sometimes referred to as disseminated sclerosis, is a slowly progressive disease of the central nervous system characterized morphologically by disseminated patches of demyelinization in the brain and spinal cord and clinically by multiple symptoms and signs with remissions and exacerbations.
The etiology of multiple sclerosis is essentially unknown and the disease has been variously attributed to: autoimmune mechanisms; infection by a slow virus; toxic agents such as metallic poisons; metabolic elements such as myelin-splitting factor; and vascular lesions resulting from abnormal blood clotting mechanisms.
Among the varied symptoms of the multiple sclerosis disease state are sensory (especially visual) disorders, spastic weakness of limbs, cerebellar ataxia, nystagmus, bladder dysfunction, mood disorders and combinations of two or more such symptoms.
Diagnosis of the disease state is virtually impossible owing to the overlap of the above-noted symptoms of multiple sclerosis and similar symptoms of other disease states. Diagnosis of the disease state is most frequently premised upon a "classic" history of remissions and exacerbations of the various symptoms over a period of years, combined with systematic elimination of other possible disease involvements which give rise to similar symptoms. Collateral testing at substantial cost and often physical discomfort to the patient is performed in order to "eliminate" e.g., intracranial lesions, cerebrovascular accidents, acoustic neuroma, cerebellar tumors, gliomas of the brain stem, spinal cord tumors, amyotrophic lateral sclerosis, syphilis, pernicious anemia, arthritis of the cervical spine, ruptured intervertebral disk, platybasia, and hereditary ataxia as the source of symptoms.
Substantial efforts have been directed toward development of diagnostic methods and materials useful in the early diagnosis of multiple sclerosis. Positive results in colloidal gold tests on cerebrospinal fluids are considered supportive, but not dispositive of, positive diagnosis. The same is true of testing for elevated gamma globulin in cerebrospinal fluids--the test tends to verify diagnosis in advanced cases but is not helpful in early diagnosis. Similarly, active demyelinization associated with the disease frequently is signified by elevation of analytical results in basic protein assay testing of spinal fluid, but test levels drop rapidly once acute exacerbation is over. Non-dispositive correlations have been made between presence of the disease state and elevated levels of measles antibodies in serum and cerebrospinal fluids. Finally, certain researchers have proposed that electron microscopic examination of lymphocytes for certain distinct morphological changes may provide a fruitful basis for diagnosis of multiple sclerosis.
The character of the most recent advances in the art is exemplified by the disclosures of Angers, et al., reported in Chemical & Engineering News, page 22, Apr. 9, 1979. Briefly summarized, Angers, et al. assert the usefulness of a leukocyte adherence inhibition (LAI) test using an essentially non-specific blood extract (so-called "Multiple Sclerosis Related Material") from the blood of multiple sclerosis patients in relapsing or progressive disease states. The LAI test involves measurement of decreasing ability of test sample erythrocytes to adhere to a glass surface after incubation in MSRM. The rather complicated, time consuming and expensive procedure is alleged to be approximately ninety percent accurate in identifying multiple sclerosis patients and 95 percent accurate in identifying non-multiple sclerosis patients.
There therefore exists a most substantial need in the art for diagnostic methods and materials for rapidly, simply and accurately determining the presence of a multiple sclerosis disease state, Desirably, such methods should be highly specific for multiple sclerosis (i.e., should not generate false positive results in the instance of other central nervous system diseases). Further, such methods should be capable of ascertaining the presence of the disease state in its early stages, should be operatively independent of disease exacerbation and remission, should not involve painful or hazardous withdrawals of patient tissue samples, and should preferrably involve standardized laboratory techniques which do not require expensive or difficult-to-operate apparatus.